Colorectal cancer (CRC) is one of the most common malignancies worldwide. The number of new cases of CRC has been increasing rapidly since 1975. More than 70% of CRC cases develop from sporadic adenomas or adenomatous polyps. Early detection and surgical removal of polyps is believed to be the most effective way to prevent benign polyps from developing into malignant tumors and thereby reducing mortality caused by CRC.
Traditional screening methods for colorectal cancer include sigmoidoscopy, fecal occult blood testing, colonscopy and double contrast barium enema. However, these traditional methods suffer from limitations and are invasive, high cost, of low predictive value or result in low detection rates. For example, WO0142504, the teachings of which are incorporated herein by reference, discloses a multi-reaction process for detection of extracellular tumor associated nucleic acid in blood plasma or serum. Further advances are desirable.
β-catenin protein was initially identified through its interaction with cadherins. Recent evidence shows that it acts as a transcriptional factor and plays a key role in the Wnt-signaling pathway Willert & Nusse, 1998). It has been demonstrated that accumulation of cytoplasmic and nuclear β-catenin signaling is tightly associated with the genesis of a wide variety of tumors. (Morin, 1999).
It has been discovered that using immunohistochemical staining that levels of nuclear β-catenin are highly correlated with he purported sequential stages in colorectal carcinogenesis with positive staining observed in 0% of normal tissues, 8% of polyps, 92% of adenomas and 100% of carcinomas. It has been further discovered that the nuclear β-catenin signal appears to clearly differentiate the polyps (non-adenomatous polyps) from adenomas (adenomatous polyps). This would be a useful marker for clinical diagnosis, or early detection of CRC, with the adenoma being considered as endpoint for risk factor. However, this diagnostic method based on the evaluation of nuclear β-catenin requires colonscopic procedure, then surgical removal of the suspected tissues.
Accordingly, there is a need for an effective, less invasive, more accurate test for early detection of cancer. The present invention meets this need.